CAR T-cell therapies have shown promise in multiple cancer types, but this study is believed to be the first test of their safety and efficacy in people with an autoimmune disease.
Immunosuppressive treatment is often a mainstay first-line therapy for MG patients, but its use often carries side effects.
“Patients with severe GMG [generalized myasthenia gravis] have limited treatment options and are often dependent on nonselective, chronic immunosuppressive therapies (ISTs) that have long-term toxicities,” Volkan Granit, the trial’s principal investigator and an assistant professor of neurology at the University of Miami Miller School of Medicine, said in a press release.
The trial’s main outcome is to determine the maximum tolerated dose after 28 days of use. A secondary goal is preliminary evidence of efficacy, as determined on the Myasthenia Gravis Activities of Daily Living scale, a test of daily activities patients are able to perform. This test will be given at the study’s start up through day 168 (about 5.6 months).
Descartes-08 is a CAR T-cell therapy, a type of treatment that involves collecting a patient’s own immune T-cells and modifying them to produce a chimeric antigen receptor, or CAR, that targets a specific protein. Descartes-08 is designed to target the BCMA (B-cell maturation antigen) protein that is found on all plasma cells, triggering their elimination to stop the production of harmful autoantibodies.
“Cartesian’s CAR-T technology selectively targets the primary culprit in the disease: antibody-producing plasma cells. Such selective targeting would be a first in GMG and could help patients discontinue use of chronic ISTs,” Granit said.
“The strategy of targeting for elimination the aberrant long-lived plasma cells that produce these autoantibodies with CAR-T cells is a novel and very promising approach,” added Michael Benatar, chief of the Neuromuscular Division at the University of Miami Miller School of Medicine, and a study co-investigator.
Importantly, the half-life — the time required to reduce the amount of a compound by half, and an indicator of how long its benefits last — of Descartes-08 is well-characterized. This allows repeat dosing of the therapy, so to maximize its potency whilst reducing the risk of toxicity.
“Unlike conventional CAR-T, which has the potential for uncontrolled proliferation and ensuing severe toxicity, Descartes-08 is engineered to have a defined and predictable half-life, enabling repeat dosing to maximize potency while minimizing risk of toxicity,” said Metin Kurtoglu, the chief medical officer at Cartesian.
Kurtoglu added that this potential therapy is also in a clinical trial for multiple myeloma.
The Phase 1/2 trial in GMG patients is due to fully conclude in April 2022.